Skip to main content
Top
Published in: Clinical Journal of Gastroenterology 5/2020

01-10-2020 | Thyrotoxicosis | Case Report

Destructive thyroiditis presenting as thyrotoxicosis followed by hypothyroidism during lenvatinib therapy for hepatocellular carcinoma

Authors: Maito Suoh, Hideki Fujii, Yuki Nagata, Kohei Kotani, Atsushi Hagihara, Masaru Enomoto, Akihiro Tamori, Masaaki Inaba, Norifumi Kawada

Published in: Clinical Journal of Gastroenterology | Issue 5/2020

Login to get access

Abstract

Hypothyroidism is a common adverse event of lenvatinib therapy for hepatocellular carcinoma (HCC), whereas thyrotoxicosis has rarely been reported in clinical trials. A 74-year-old man complaining of abdominal pain was found to have liver tumors and paraaortic lymphadenopathy. The intrahepatic lesions were diagnosed as HCC by angiography and treated with transcatheter arterial chemoembolization. Although localized prostate cancer was discovered incidentally, the etiology of paraaortic lymphadenopathy was assumed to be metastatic HCC. Lenvatinib 12 mg/day was started when his thyroid function tests were almost normal but was interrupted because of thyrotoxicosis. The patient was negative for tested thyroid autoantibodies. Color Doppler ultrasonography detected reduced thyroid blood flow, suggesting destructive thyroiditis. Although he resumed lenvatinib at 8 mg/day once his serum level of free thyroxine normalized, thyrotoxicosis recurred. Subsequently, he suffered hypothyroidism, which exacerbated despite levothyroxine replacement. Lenvatinib was discontinued as it was ineffective against the paraaortic lymph node metastasis, and external-beam radiotherapy was performed. After the completion of radiotherapy, the thyroid dysfunction significantly improved. In summary, lenvatinib for HCC can induce transient thyrotoxicosis followed by hypothyroidism, which is compatible with destructive thyroiditis. During lenvatinib therapy, close monitoring of thyroid function and appropriate management of thyrotoxicosis as well as hypothyroidism are essential.
Literature
1.
go back to reference Matsui J, Yamamoto Y, Funahashi Y, et al. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer. 2008;122:664–71.CrossRef Matsui J, Yamamoto Y, Funahashi Y, et al. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer. 2008;122:664–71.CrossRef
2.
go back to reference Yamamoto Y, Matsui J, Matsushima T, et al. Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage. Vasc Cell. 2014;6:18.CrossRef Yamamoto Y, Matsui J, Matsushima T, et al. Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage. Vasc Cell. 2014;6:18.CrossRef
3.
go back to reference Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial. Lancet. 2018;391:1163–73.CrossRef Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial. Lancet. 2018;391:1163–73.CrossRef
4.
go back to reference European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69:182–236.CrossRef European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69:182–236.CrossRef
5.
go back to reference Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723–50.CrossRef Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723–50.CrossRef
6.
go back to reference Ikeda K, Kudo M, Kawazoe S, et al. Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma. J Gastroenterol. 2017;52:512–9.CrossRef Ikeda K, Kudo M, Kawazoe S, et al. Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma. J Gastroenterol. 2017;52:512–9.CrossRef
7.
go back to reference Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26:1343–421.CrossRef Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26:1343–421.CrossRef
8.
go back to reference Sakurai K, Fukazawa H, Arihara Z, et al. Sunitinib-induced thyrotoxicosis followed by persistent hypothyroidism with shrinkage of thyroid volume. Tohoku J Exp Med. 2010;222:39–44.CrossRef Sakurai K, Fukazawa H, Arihara Z, et al. Sunitinib-induced thyrotoxicosis followed by persistent hypothyroidism with shrinkage of thyroid volume. Tohoku J Exp Med. 2010;222:39–44.CrossRef
9.
go back to reference van Doorn L, Eskens FA, Visser TJ, et al. Sorafenib induced thyroiditis in two patients with hepatocellular carcinoma. Thyroid. 2011;21:197–202.CrossRef van Doorn L, Eskens FA, Visser TJ, et al. Sorafenib induced thyroiditis in two patients with hepatocellular carcinoma. Thyroid. 2011;21:197–202.CrossRef
10.
go back to reference Makita N, Iiri T. Tyrosine kinase inhibitor-induced thyroid disorders: a review and hypothesis. Thyroid. 2013;23:151–9.CrossRef Makita N, Iiri T. Tyrosine kinase inhibitor-induced thyroid disorders: a review and hypothesis. Thyroid. 2013;23:151–9.CrossRef
11.
go back to reference Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med. 2003;348:2646–55.CrossRef Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med. 2003;348:2646–55.CrossRef
12.
go back to reference Hirooka M, Ochi H, Hiraoka A, et al. Destructive thyroiditis induced by lenvatinib in three patients with hepatocellular carcinoma. Intern Med. 2019;58:791–5.CrossRef Hirooka M, Ochi H, Hiraoka A, et al. Destructive thyroiditis induced by lenvatinib in three patients with hepatocellular carcinoma. Intern Med. 2019;58:791–5.CrossRef
14.
go back to reference Ota H, Amino N, Morita S, et al. Quantitative measurement of thyroid blood flow for differentiation of painless thyroiditis from Graves’ disease. Clin Endocrinol (Oxf). 2007;67:41–5.CrossRef Ota H, Amino N, Morita S, et al. Quantitative measurement of thyroid blood flow for differentiation of painless thyroiditis from Graves’ disease. Clin Endocrinol (Oxf). 2007;67:41–5.CrossRef
15.
go back to reference Hari Kumar KV, Pasupuleti V, Jayaraman M, et al. Role of thyroid Doppler in differential diagnosis of thyrotoxicosis. Endocr Pract. 2009;15:6–9.CrossRef Hari Kumar KV, Pasupuleti V, Jayaraman M, et al. Role of thyroid Doppler in differential diagnosis of thyrotoxicosis. Endocr Pract. 2009;15:6–9.CrossRef
16.
go back to reference Donkol RH, Nada AM, Boughattas S. Role of color Doppler in differentiation of Graves’ disease and thyroiditis in thyrotoxicosis. World J Radiol. 2013;5:178–83.CrossRef Donkol RH, Nada AM, Boughattas S. Role of color Doppler in differentiation of Graves’ disease and thyroiditis in thyrotoxicosis. World J Radiol. 2013;5:178–83.CrossRef
18.
go back to reference Koizumi Y, Hirooka M, Hiraoka A, et al. Lenvatinib-induced thyroid abnormalities in unresectable hepatocellular carcinoma. Endocr J. 2019;66:787–92.CrossRef Koizumi Y, Hirooka M, Hiraoka A, et al. Lenvatinib-induced thyroid abnormalities in unresectable hepatocellular carcinoma. Endocr J. 2019;66:787–92.CrossRef
19.
go back to reference Torino F, Corsello SM, Longo R, et al. Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy. Nat Rev Clin Oncol. 2009;6:219–28.CrossRef Torino F, Corsello SM, Longo R, et al. Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy. Nat Rev Clin Oncol. 2009;6:219–28.CrossRef
20.
go back to reference Drui D, Illouz F, Do Cao C, et al. Expert opinion on thyroid complications of new anticancer therapies: tyrosine kinase inhibitors. Ann Endocrinol (Paris). 2018;79:569–73.CrossRef Drui D, Illouz F, Do Cao C, et al. Expert opinion on thyroid complications of new anticancer therapies: tyrosine kinase inhibitors. Ann Endocrinol (Paris). 2018;79:569–73.CrossRef
21.
go back to reference Ikeda M, Kobayashi M, Tahara M, et al. Optimal management of patients with hepatocellular carcinoma treated with lenvatinib. Expert Opin Drug Saf. 2018;17:1095–105.CrossRef Ikeda M, Kobayashi M, Tahara M, et al. Optimal management of patients with hepatocellular carcinoma treated with lenvatinib. Expert Opin Drug Saf. 2018;17:1095–105.CrossRef
22.
go back to reference Tada T, Kumada T, Hiraoka A, et al. Safety and efficacy of lenvatinib in elderly patients with unresectable hepatocellular carcinoma: a multicenter analysis with propensity score matching. Hepatol Res. 2020;50:75–83.CrossRef Tada T, Kumada T, Hiraoka A, et al. Safety and efficacy of lenvatinib in elderly patients with unresectable hepatocellular carcinoma: a multicenter analysis with propensity score matching. Hepatol Res. 2020;50:75–83.CrossRef
23.
24.
go back to reference Kamba T, Tam BY, Hashizume H, et al. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol. 2006;290:H560–H576576.CrossRef Kamba T, Tam BY, Hashizume H, et al. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol. 2006;290:H560–H576576.CrossRef
25.
go back to reference Yang Y, Zhang Y, Cao Z, et al. Anti-VEGF- and anti-VEGF receptor-induced vascular alteration in mouse healthy tissues. Proc Natl Acad Sci USA. 2013;110:12018–23.CrossRef Yang Y, Zhang Y, Cao Z, et al. Anti-VEGF- and anti-VEGF receptor-induced vascular alteration in mouse healthy tissues. Proc Natl Acad Sci USA. 2013;110:12018–23.CrossRef
26.
go back to reference Turner N, Grose R. Fibroblast growth factor signalling: From development to cancer. Nat Rev Cancer. 2010;10:116–29.CrossRef Turner N, Grose R. Fibroblast growth factor signalling: From development to cancer. Nat Rev Cancer. 2010;10:116–29.CrossRef
27.
go back to reference Hughes SE. Differential expression of the fibroblast growth factor receptor (FGFR) multigene family in normal human adult tissues. J Histochem Cytochem. 1997;45:1005–199.CrossRef Hughes SE. Differential expression of the fibroblast growth factor receptor (FGFR) multigene family in normal human adult tissues. J Histochem Cytochem. 1997;45:1005–199.CrossRef
28.
go back to reference St Bernard R, Zheng L, Liu W, et al. Fibroblast growth factor receptors as molecular targets in thyroid carcinoma. Endocrinology. 2005;146:1145–53.CrossRef St Bernard R, Zheng L, Liu W, et al. Fibroblast growth factor receptors as molecular targets in thyroid carcinoma. Endocrinology. 2005;146:1145–53.CrossRef
29.
go back to reference Shinohara N, Takahashi M, Kamishima T, et al. The incidence and mechanism of sunitinib-induced thyroid atrophy in patients with metastatic renal cell carcinoma. Br J Cancer. 2011;104:241–7.CrossRef Shinohara N, Takahashi M, Kamishima T, et al. The incidence and mechanism of sunitinib-induced thyroid atrophy in patients with metastatic renal cell carcinoma. Br J Cancer. 2011;104:241–7.CrossRef
30.
go back to reference Kitajima K, Takahashi S, Maeda T, et al. Thyroid size change by CT monitoring after sorafenib or sunitinib treatment in patients with renal cell carcinoma: Comparison with thyroid function. Eur J Radiol. 2012;81:2060–5.CrossRef Kitajima K, Takahashi S, Maeda T, et al. Thyroid size change by CT monitoring after sorafenib or sunitinib treatment in patients with renal cell carcinoma: Comparison with thyroid function. Eur J Radiol. 2012;81:2060–5.CrossRef
31.
go back to reference Riesenbeck LM, Bierer S, Hoffmeister I, et al. Hypothyroidism correlates with a better prognosis in metastatic renal cancer patients treated with sorafenib or sunitinib. World J Urol. 2011;29:807–13.CrossRef Riesenbeck LM, Bierer S, Hoffmeister I, et al. Hypothyroidism correlates with a better prognosis in metastatic renal cancer patients treated with sorafenib or sunitinib. World J Urol. 2011;29:807–13.CrossRef
32.
go back to reference Clemons J, Gao D, Naam M, et al. Thyroid dysfunction in patients treated with sunitinib or sorafenib. Clin Genitourin Cancer. 2012;10:225–31.CrossRef Clemons J, Gao D, Naam M, et al. Thyroid dysfunction in patients treated with sunitinib or sorafenib. Clin Genitourin Cancer. 2012;10:225–31.CrossRef
33.
go back to reference Schmidinger M, Vogl UM, Bojic M, et al. Hypothyroidism in patients with renal cell carcinoma: blessing or curse? Cancer. 2011;117:534–44.CrossRef Schmidinger M, Vogl UM, Bojic M, et al. Hypothyroidism in patients with renal cell carcinoma: blessing or curse? Cancer. 2011;117:534–44.CrossRef
34.
go back to reference Beukhof CM, van Doorn L, Visser TJ, et al. Sorafenib-induced changes in thyroid hormone levels in patients treated for hepatocellular carcinoma. J Clin Endocrinol Metab. 2017;102:2922–9.CrossRef Beukhof CM, van Doorn L, Visser TJ, et al. Sorafenib-induced changes in thyroid hormone levels in patients treated for hepatocellular carcinoma. J Clin Endocrinol Metab. 2017;102:2922–9.CrossRef
35.
go back to reference Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52–60.CrossRef Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52–60.CrossRef
Metadata
Title
Destructive thyroiditis presenting as thyrotoxicosis followed by hypothyroidism during lenvatinib therapy for hepatocellular carcinoma
Authors
Maito Suoh
Hideki Fujii
Yuki Nagata
Kohei Kotani
Atsushi Hagihara
Masaru Enomoto
Akihiro Tamori
Masaaki Inaba
Norifumi Kawada
Publication date
01-10-2020
Publisher
Springer Singapore
Published in
Clinical Journal of Gastroenterology / Issue 5/2020
Print ISSN: 1865-7257
Electronic ISSN: 1865-7265
DOI
https://doi.org/10.1007/s12328-020-01107-6

Other articles of this Issue 5/2020

Clinical Journal of Gastroenterology 5/2020 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.